This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Regulation of key events in almost every cellular process - from cell signaling to targeted protein degradation or DNA repair - requires specific intermolecular interactions that alter the location or activity of effector proteins. It is now clear that most of these interactions are driven by one or more binding 'domains'or 'modules', which work alone or in concert to define the molecular recognition properties of a particular proteins. There are also several classes of domain that bind membrane phospholipids instead of (or in addition to) protein targets. In particular, a few membrane-targeting modules recognize specific phosphoinositides in cellular membranes, and play an important role in cellular signaling, membrane trafficking, cytoskeletal organization, and other cellular functions. F-BAR domains have become known as domains the bind (or sense) curved membranes, and we have found that the yeast Rho-GAP Rgd1p has a PtdIns(4,5)P2-specific F-BAR domain. This research is designed to address the mechanism of PtdIns(4,5)P2 recognition by providing the first structural view of any BAR/F-BAR domain family member in complex with a lipid binding target.